发现具有针对SARS-CoV-2的抗病毒活性的C链接核酸类型
Eugen F Mesaros1, Benjamin J Dugan1, Min Gao1
1Arbutus Biopharma, Inc., 701 Veterans Circle, Warminster, Pennsylvania 18974, United States.
ACS infectious diseases
|April 23, 2024
概括
研究人员确定了新型核糖类类似物10e和10n作为SARS-CoV-2 nsp12RNA依赖RNA聚合酶的强有力的抑制剂,为急性呼吸道RNA病毒感染提供了潜在的新疗法.
科学领域:
- 病毒学 病毒学
- 药用化学 医学化学
- 药物发现 药物发现 药物发现
背景情况:
- 随着COVID-19的爆发,人们越来越需要针对急性呼吸道RNA病毒感染的抗病毒疗法.
- 目前的直接作用抗病毒治疗有局限性,需要对新药进行研究.
- 已批准的药物如尼尔马特里尔维尔,恩西特里尔维尔,雷梅西维尔和莫尔努皮拉维尔有希望,但需要进一步开发以提高有效性和安全性.
研究的目的:
- 为了确定针对冠状病毒的NSP12RNA依赖RNA聚合酶的新型抑制剂.
- 开发具有提高功效,代谢稳定性,降低耐药性和毒性风险的核酸类相应物.
- 评估新合成化合物的泛冠状病毒活性和作用机制.
主要方法:
- 新型核酸相似物的合成和化学表征.
- 在实验室中对泛冠状病毒活性进行细胞感染查.
- 细胞化研究,以评估代谢转化到活性三酸盐核酸.
- 生物化学测定以确认与nsp12的目标接触.
主要成果:
- 已识别出核酸类似物10e和10n,具有有利的泛冠状病毒活性.
- 在基于细胞的测试中,证明了化合物10e和10n的代谢转化为活性三酸核酸.
- 通过生物化学测定,确认了被识别的抑制剂对nsp12的直接向激活.
结论:
- 核类型10e和10n是新型冠状病毒抗病毒疗法的有希望的候选者.
- 这些化合物显示出有效抑制病毒nsp12聚合酶.
- 需要进一步的研究,以优化这些药物用于临床开发,以对抗急性呼吸道RNA病毒感染.
更多相关视频
相关概念视频
Subviral Agents
Subviral agents are infectious entities that resemble viruses but lack one or more viral components, such as a capsid or essential replication machinery. These agents include viroids, prions, and satellites, each possessing distinct structural and functional characteristics that influence their mode of infection and replication.Viroids are the simplest subviral agents, consisting of circular, single-stranded RNA molecules without a protein coat. They exclusively infect plants, relying entirely...
Coronavirus
Coronaviruses, including the severe acute respiratory syndrome coronavirus (SARS-CoV), are enveloped viruses characterized by their single-stranded, positive-sense RNA genome and helical nucleocapsid structure. The hallmark of these viruses is their club-shaped spike (S) glycoproteins that protrude from the viral envelope, facilitating attachment to host cells. Typically, coronaviruses infect the upper respiratory tract, often causing mild or asymptomatic disease. However, certain strains like...
Inhibitors of Viral Protein Synthesis
Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
Inhibitors Of Virion Release
Viral replication and dissemination rely on efficient mechanisms for host cell entry, genome replication, assembly, and release. Influenza viruses, such as types A and B, are negative-sense single-stranded RNA viruses with a segmented genome, that depend on two critical surface glycoproteins to carry out these processes: hemagglutinin (HA) and neuraminidase (NA). HA initiates infection by binding to sialic acid residues on the surface of host epithelial cells, facilitating receptor-mediated...
Antiviral Nucleoside Inhibitors
Antiviral Nucleoside InhibitorsAntiviral nucleoside inhibitors are structural analogs of natural nucleosides that interfere with viral DNA or RNA synthesis. These compounds selectively target viral polymerases due to their resemblance to host nucleosides, thereby disrupting viral genome replication.Mechanism of Acyclovir ActionAcyclovir is a guanosine analog with a three-carbon acyclic side chain. It selectively targets herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2),...
Inhibitors of Virion Maturation and Assembly
As part of their replication cycle, certain viruses synthesize long precursor proteins called polyproteins within infected host cells. In human immunodeficiency virus (HIV), two major polyproteins are produced: Gag and Gag-Pol. The Gag polyprotein supplies the structural components of the virus, while Gag-Pol includes essential viral enzymes such as reverse transcriptase, integrase, and protease. After synthesis, these polyproteins move to the host cell membrane, where they assemble into an...


